Magnetically vectored platforms for the targeted delivery of therapeutics to tumors: history and current status.

Superparamagnetic iron oxide nanoparticles (SPIONs) are being developed as vehicles for the selective targeting of therapeutics and bioactive compounds. Presented herein is a brief review of the history of approaches to magnetic-based drug delivery platforms, leading to current concepts of magnetically vectored therapeutics via functionalized SPION-prodrugs. With this background, recent experimental results are discussed that demonstrate the use of shaped external magnetic field gradients, generated by designed configurations of permanent magnets, to drive the concentration/accumulation of modified SPION-prodrug constructs at a tumor site, followed by tumor extravasation and activation of the prodrug within the tumor microenvironment. In order to successfully translate this approach to clinical application, one of the key requirements is the ability to magnetically drive ('vector') the SPION to human-scale tumor settings. In this review, various configurations of permanent magnets are described and models are presented that demonstrate that magnetic field gradients can potentially be focused and extended to lengths of several inches in vivo. This modification thereby increases the range of the delivery platform, and offers the potential for the treatment of visceral as well as superficial tumors and for translation from preclinical animal tumor models to clinical settings. The methodology of magnetically vectored prodrug therapeutics, as a means for selective localized targeting of tumor tissue, and minimizing harm to normal tissue, has the additional advantage of raising the therapeutic index compared with that of free drugs, thus, offering great potential as a cancer treatment modality.